Reply:
Authors: Anna Glantz, Hanns-Ulrich Marschall, Lars-Åke Mattsson
Journal: Hepatology (2005)

We thank Dr. Sentilhes and coworkers for their interest in the results from the observational part of the Swedish ICP study, in which we demonstrated that fetal risk correlated with maternal bile acid levels. We stratified a large patient material (n = 690) of pregnant women with pruritus into three groups: no ICP (serum bile acids <10μmol/L), mild ICP (10-39 μmol/L) and severe ICP (≥40μmol/L). Spontaneous preterm delivery; asphyxial events (operative delivery due to asphyxia, arterial umbilical pH <7.05, or Apgar score <7 at 5 minutes); and meconium staining of amniotic fluid, placenta, and membranes were found to be significantly increased in the group with severe ICP compared with the groups with no ICP and mild ICP. No differences in these variables were detected between the group with no ICP and the group with mild ICP. Furthermore, a higher frequency of intrauterine fetal death (IUFD) in prior pregnancies was reported by women in the group with severe ICP (4.1%) compared with the groups with no ICP (0.6%) and mild ICP (0.8%) (P < .001). The rates of IUFD in the group with no ICP and the group with mild ICP did not differ significantly from the overall IUFD rate in Sweden (0.4%). In their comments, our French colleagues referred to the fact that one of our IUFD cases had bile acid levels below 40 μmol/L (27 μmol/L). This case was a twin pregnancy, in which one fetus died and the other survived. At delivery, a tight knot on the umbilical cord of the dead twin was found. Fetuses in twin pregnancies are indeed exposed to a higher risk, and all cases of IUFD in ICP pregnancies are not necessarily related to the disease. A recent study by Williamson et al.1 investigated fetal outcome in women with ICP, and they reported high fetal complication rates. However, in this study several confounding factors were present. Their patient material was based on a questionnaire survey in women with ICP that were identified by a patient support group. As the authors themselves stated in the article, this fact may indicate that the material was enriched by pregnancies in which complications had occurred. It should be pointed out that induction of labor, especially before term, is associated with an increase of fetal and maternal risk in terms of prolonged labor, higher frequencies of emergency cesarean section, and fetal asphyxia. We agree that the slight increase in risk of respiratory distress syndrome in the neonate is not an important issue when deciding to induce labor. Nevertheless, it should be underlined that inductions of labor should be conducted only in cases in which benefits outweigh risks. Our study proved that fetuses in pregnant women with bile acid levels exceeding 40 μmol/L were exposed to an increased risk, and in this group it seems reasonable to propose active management (pharmacological treatment or induction of labor). Because we could not find any increase of fetal risk in our large study population of women with ICP and bile acid levels 10 to 39 μmol/L, we cannot find any evidence to support that these women would benefit from routine induction before term. To further address this issue, a randomized study between active and expectant management should be conducted in this specific group. Anna Glantz M.D.*, Hanns-Ulrich Marschall M.D. Ph.D.*, Lars-Åke Mattsson M.D., Ph.D.*, * Dept of Obstetrics/Gynaecology, Sahlgrenska University Hospital/East, Göteborg, Sweden.